title: Inflammation, obesity, and thrombosis.
abstract: Clinical and epidemiological studies support a connection between obesity and thrombosis, involving elevated expression of the prothrombotic molecules plasminogen activator inhibitor-1 and tissue factor (TF) and increased platelet activation. Cardiovascular diseases and metabolic syndrome-associated disorders, including obesity, insulin resistance, type 2 diabetes, and hepatic steatosis, involve inflammation elicited by infiltration and activation of immune cells, particularly macrophages, into adipose tissue. Although TF has been clearly linked to a procoagulant state in obesity, emerging genetic and pharmacologic evidence indicate that TF signaling via G protein-coupled protease-activated receptors (PAR2, PAR1) additionally drives multiple aspects of the metabolic syndrome. TF-PAR2 signaling in adipocytes contributes to diet-induced obesity by decreasing metabolism and energy expenditure, whereas TF-PAR2 signaling in hematopoietic and myeloid cells drives adipose tissue inflammation, hepatic steatosis, and insulin resistance. TF-initiated coagulation leading to thrombin-PAR1 signaling also contributes to diet-induced hepatic steatosis and inflammation in certain models. Thus, in obese patients, clinical markers of a prothrombotic state may indicate a risk for the development of complications of the metabolic syndrome. Furthermore, TF-induced signaling could provide new therapeutic targets for drug development at the intersection between obesity, inflammation, and thrombosis.
authors.affiliation: Department of Cell Biology, Torrey Pines Institute for Molecular Studies, San Diego, CA; and.
authors.forename: Fahumiya
authors.initials: F
authors.lastname: Samad
authors.forename: Wolfram
authors.initials: W
authors.lastname: Ruf
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000503:physiopathology; D051379:Mice; D008820:Mice, Obese; D008954:Models, Biological; D009765:Obesity / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology*; D044463:Receptor, PAR-1 / Q000502:physiology; D044464:Receptor, PAR-2 / Q000502:physiology; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D019851:Thrombophilia / Q000209:etiology* / Q000503:physiopathology; D013925:Thromboplastin / Q000502:physiology*; D013927:Thrombosis / Q000209:etiology* / Q000503:physiopathology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; C051321:SERPINE1 protein, human; D013925:Thromboplastin